Efficacy & safety of continuous erythropoietin receptor activator (CERA) in treating renal anaemia in diabetic patients with chronic kidney disease not on dialysis.

Background & objectives: Chronic kidney disease (CKD) patients on dialysis regularly receive erythropoiesis stimulating agent (ESA) for treating renal anaemia during their dialysis unlike those who are not on dialysis. In such patients, the longer acting ESA can be helpful in reducing their frequent visits to the health care facilities and improving their compliance. This study was aimed to examine the efficacy and safety of continuous erythropoietin receptor activator (CERA), a long acting ESA in treating renal anaemia in patients with diabetic CKD not on dialysis. Methods: In this prospective, open-labelled, pilot clinical study, 35 adult type 2 diabetes patients with nephropathy and renal anaemia, who were not on dialysis nor receiving treatment with ESA were administered CERA subcutaneously once in two weeks for a period of 24 weeks. The primary efficacy end point was to evaluate the Hb response (Hb rise of ≥1 g/dl above the baseline or Hb level ≥11 g/dl) during the study period. Results: All patients showed Hb rise ≥1 g/dl during the study period and 80 per cent patients could achieve Hb value ≥11 g/dl. The maximum median Hb rise of 1.2 g/dl occurred in the initial 6 weeks after starting the treatment. The mean creatinine clearance (CrCl) improved by 2.8 ml/min, with mean Hb rise of 2.6 g/dl from the baseline after administration of CERA. Worsening of blood pressure (BP) control (42.9%) was the most common adverse event. Interpretation & conclusions: CERA once in two weeks was found to be efficacious in correcting anaemia in the ESA-naïve patients with diabetic nephropathy who are not on dialysis. However, regular monitoring of blood pressure is required while on treatment with CERA.

Correction of Anemia with Continuous Erythropoietin Receptor Activator in Korean Patients on Long-Term Hemodialysis

Continuous erythropoietin receptor activator (CERA) is an erythropoietin with a long-half life. This study investigated the efficacy of CERA for correcting anemia in Korean patients on dialysis. Patients (> or =18 yr) who were not receiving any ESAs for more than 8 weeks were randomly assigned to either intravenous CERA once every 2 weeks (n=39) or epoetin beta thrice-weekly (n=41) during a 24-week correction phase. Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL and Hb> or =11 g/dL without red blood cell (RBC) transfusion. Median dialysis duration was 1.7 (0.3-20.8) and 1.6 (0.4-13.8) yr in CERA and epoetin beta group, respectively. Hemoglobin response rate of CERA was 79.5% (95% confidence interval [CI], 63.5-90.7). As the lower limit of 95% CI was higher than pre-specified 60% response rate, it can be concluded that CERA corrected anemia (P<0.05). Hb response rate of epoetin beta was 87.8% (95% CI, 73.8-95.9) (P=0.37). Median time to response was 12 weeks in CERA and 10.3 weeks in epoetin beta (P=0.03). It is suggested that once every 2 weeks administration of CERA is effective for correcting anemia in Korean patients on long-term hemodialysis with longer time-to-response than thrice weekly epoetin beta. (ClinicalTrials.gov registry No. NCT00546481)

Efficacy,safety and tolerance of continuous erythropoietin receptor activator intravenous administration on anemia correction in dialysis patients with chronic renal anemia / 中华肾脏病杂志

Objective To evaluate the efficacy,safety and tolerance of continuous erythropoietin receptor activator (CERA) once every 2 weeks intravenous injection on anemia correction in dialysis patients compared to Epoetin-3 (EPO-β) administration.Methods An open-label,randomized,parallel,active-control and multi-center clinical trial was performed.All the hemodialysis or peritoneal dialysis patients with chronic renal anemia who had not been treated with erythropoiesis-stimulating agents (ESAs)for at least 8 weeks before entering the treatment phase were randomized (1∶1) to receive either CERA once every 2 weeks intravenous administration (CERA group,n=132) or intravenous EPO-β three times weekly (EPO group,n=133) for 24 weeks including 16-week correction period and 8-week efficacy evaluation period.At week 25,the patients who reached the target Hb (defined as Hb≥ 110 g/L and increase in Hb≥10 g/L from baseline without red blood cell transfusion during the 24 weeks after the first dose) were kept on CERA or EPO-β treatment regimen for the subsequent 28 weeks to evaluate the long-term safety and tolerability.The starting dose of CERA was 0.4 μg/kg.Two primary endpoints were (1) the Hb response rate during the first 24 weeks; and (2)the mean change in Hb between the baseline and the evaluation periods (week 17 to week 24).Results Totally 232 patients (87.5％) completed the first 24-week treatment and 198 patients (74.7％) completed the whole study treatment (52 weeks).The response rate in CERA group during the first 24 weeks was 87.12％[95％ CI(80.2％ to 92.3％)].Since the lower limit of the 95％CI was greater than 60％ (P ＜ 0.01),CERA once every 2 weeks intravenous administration was considered as effective in correction of renal anemia.The difference between CERA group and EPO group in mean change of Hb from evaluation periods to baseline in the per-protocol (PP) population was-4.7 g/L [95％CI (-7.38 g/L to-1.92 g/L)].Since the lower limit of 95％CI was greater than the pre-defined noninferiority margin-7.5 g/L (P=0.0205),CERA was considered as non-inferior to EPO in the maintenance of Hb after anemia correction.The Hb level remained stable during the subsequent 28-week extension period in both CERA and EPO groups.During the whole study period,the overall safety findings were similar in CERA and EPO groups,50.0％ and 54.6％ of patients experienced at least one adverse event (AE) respectively.The findings from AEs were in accordance with the characteristics of the studied population.Conclusions Intravenous CERA once every 2 weeks is safe and effective for correcting anemia in dialysis patients.Treatment with CERA once every 2 weeks is also non-inferior to 3 times weekly EPO in maintaining the Hb level after the correction.In general,long-term intravenous administration of CERA is well tolerated by dialysis patients with chronic renal anemia.

The efficacy and safety of continuous erythropoietin receptor activator in dialytic patients with chronic renal anemia: an open, randomized, controlled, multi-center trial / 中华内科杂志

Objective To evaluate the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) once every 4 weeks by subcutaneous administration on hemoglobin (Hb)maintenance in dialytic patients with chronic renal anemia who had been treated with stable dose of erythropoietin (EPO).Methods This was an open,randomized,controlled,multi-center trial.All the hemodialysis or peritoneal dialytic patients in EPO maintenance treatment received subcutaneous EPO-β during the 6-week pre-treatment period to maintain Hb level between 100 g/L and 120 g/L.Eligible patients were randomized (2∶1 ) to accept either C.E.R.A.once every 4 weeks by subcutaneous administration ( C.E.R.A.group,n =187 ) or subcutaneous EPO-β 1-3 times weekly ( EPO group,n =94) for 28 weeks (including 20-week dose titration period and 8-week efficacy evaluation period ). The starting dose of C.E.R.A.was converted according to the dose of EPO-β administered in the week preceding the first study drug administration.The primary outcome was the change of Hb level between the baseline and that in the efficacy evaluation period.Results Totally 253 patients completed the whole 28-week treatment.The change of baseline-adjusted mean Hb was +2.57 g/L for C.E.R.A.group and + 1.23 g/L for EPO group,resulting in a treatment difference of 1.34 g/L (95％ CI - 1.11-3.78 g/L).Since the lower limit of 95％ CI was greater than the pre-defined non-inferiority margin -7.5 g/L( P ＜ 0.0001 ),C.E.R.A.once every 4 weeks by subcutaneous administration was clinically non-inferior to EPO regarding the maintenance of stable Hb level.The proportion of patients maintaining Hb level within the range of 100-120 g/L through efficacy evaluation period was similar between the two groups ( 69.0％ for C.E.R.A.group vs 68.9％ for EPO group,P ＞0.05 ).The overall incidence of adverse events was similar between the C.E.R.A.(41.7％)and EPO (46.2％ ) groups ( P ＞ 0.05 ).The safety findings were in accordance with the patients' primary diseases rather than the administration.Conclusions Conversion from EPO to C.E.R.A.once every 4 weeks by subcutaneous injection could maintain the Hb in target level in dialytic patients with renal anemia,and it was non-inferior to EPO.In general,subcutaneous administration of C.E.R.A.is well tolerated in dialytic patients with chronic renal anemia.